The increased incidence of myocardial infarct in diabetic individuals is also associated with poor prognosis. The reason for this is not clear, but probably is related to microvascular disease and to alterations in myocardial metabolism. There is some evidence that the contribution of endogenous glycogen to anaerobic glycolysis during anoxia may be one important factor which determines whether or not diabetic myocardium will survive an infarct. However, little information is available regarding the role of glycogenolysis in protecting diabetic myocardium. This project will provide a detailed examination of changes in cyclic AMP and cyclic GMP concentrations, as well as protein kinase, phosphorylase kinase, phosphorylase and glycogen synthase activation states. It will be determined if the activation sequence is altered in the diabetic state in either the presence of anoxic or beta-adrenergic receptor stimulation of glycogenolysis. Changes in this sequence in diabetic or normal myocardium will be correlated with the onset and recovery from an anoxic insult in the presence or absence of interventions known to alter recovery. The information gained will not only provide basic understanding of the regulation of glycogen metabolism in the diabetic heart but will also allow for a more rational approach to supporting the heart under conditions of anoxia or ischemia.